Universal Screening Modestly Ups Lynch Syndrome Diagnosis

(HealthDay News) – In patients with colorectal cancer, universal testing for mutations in genes associated with Lynch syndrome, the most common form of hereditary colorectal cancer, has modestly better diagnostic sensitivity than other strategies, according to a study published in the Oct. 17 issue of the Journal of the American Medical Association.

Leticia Moreira, M.D., from the University of Barcelona in Spain, and colleagues compared four strategies to identify carriers of germline mutations in DNA mismatch repair (MMR) genes among 10,206 unrelated patients newly diagnosed with colorectal cancer: Bethesda guidelines; Jerusalem recommendations; those derived from an analysis of variables associated with Lynch syndrome; and tumor MMR testing or germline MMR gene analysis of all colorectal cancer patients (universal screening).

The researchers found that 3.1 percent were carriers of MMR germline mutations. Universal screening of tumor MMR genes yielded 100 percent sensitivity, 93 percent specificity, and a diagnostic yield of 2.2 percent. In contrast, the sensitivity of other approaches ranged from 85.4 to 95.1 percent, and the other approaches produced diagnostic yields ranging from 1.9 to 2.1 percent. The best selective strategy missed 4.9 percent of Lynch syndrome cases and, compared with the universal approach, led to a 34.8 percent reduction in patients requiring tumor MMR testing and a 28.6 percent reduction in patients requiring germline mutational analysis.

"Universal tumor MMR testing among colorectal cancer probands had a greater sensitivity for the identification of Lynch syndrome compared with multiple alternative strategies, although the increase in the diagnostic yield was modest," Moreira and colleagues conclude.